title: Different orientations of low-molecular-weight fragments in the binding pocket of a BRD4 bromodomain.
abstract: Bromodomains are involved in the regulation of chromatin architecture and transcription through the recognition of acetylated lysines in histones and other proteins. Many of them are considered to be relevant pharmacological targets for different pathologies. Three crystallographic structures of the N-terminal bromodomain of BRD4 in complex with low-molecular-weight fragments are presented. They show that similar molecules mimicking acetylated lysine bind the bromodomain with different orientations and exploit different interactions. It is also advised to avoid DMSO when searching for low-affinity fragments that interact with bromodomains since DMSO binds in the acetylated lysine-recognition pocket of BRD4.
authors.affiliation: Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy.
authors.forename: Graziano
authors.initials: G
authors.lastname: Lolli
authors.forename: Roberto
authors.initials: R
authors.lastname: Battistutta
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins; D018360:Crystallography, X-Ray; D006801:Humans; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins
keywords: BRD4; bromodomains; low-molecular-weight fragments